Project Summary: Project 2, Neural Coding and Dynamics in Neocortical Regions Working memory, the ability to temporarily hold multiple pieces of information in mind for manipulation, is central to virtually all cognitive abilities. This multi-component research project aims to comprehensively dissect the neural circuit mechanisms of this ability during a working memory and decision task based on accumulation of sensory evidence. Inactivation experiments in another component of the project will identify participating brain areas and their particular roles in such tasks. The goal of this project is to characterize the neural coding and dynamics in the neocortical brain areas found to have a causal role in the behavior. Initial inactivation results suggest that much of neocortex is involved. Thus, the project will produce a broad survey of neocortex using cellular-resolution calcium imaging with the most advanced optical-imaging technology, like the mesoscope. The results of this survey will be a dataset, unprecedented in the field of working memory and decision-making, that will greatly illuminate the nature of each region?s potential contributions and their computations. In parallel, neocortical dynamics will be measured with cell-type specificity, starting with populations of inhibitory neurons. Preliminary data shows choice-specific sequences and cue-locked cells in neocortical pyramidal neurons in six brain regions during an evidence-accumulation task involving navigation in virtual reality, but it is unclear whether these kinds of activity are specific to preliminary experiments or will generalize to diverse evidence-accumulation behaviors. To address this question, researchers will apply two-photon, cellular-resolution calcium imaging during other evidence-accumulation tasks, to explore the dependence on species (rat vs. mouse), behavioral readout (T-maze navigation vs. orienting vs. right/left licking), or sensory modality (towers, light flashes, airpuffs). The survey of neocortical activity at cellular resolution will be done one or a few areas at a time. Finally, the project will use widefield imaging fluorescence macroscopes, including a novel head-mounted version, for simultaneous imaging of all dorsal cortical areas during evidence-accumulation tasks. The maps will identify, for the first time, the simultaneously acquired spatial and temporal structure of region activation across the neocortical surface during an evidence-accumulation task in rodents. Based on the preliminary data, this work, along with the imaging results obtained in another project component, is expected to produce the most detailed information available to date on brain-wide activity, at cellular resolution, during performance of a cognitive task. Ultimately, these results will be used, in conjunction with perturbation and interaction data from other parts of the project, to develop and constrain biophysically realistic models of the neural mechanisms underlying working memory and decision-making across multiple brain areas.